In case you are not already familiar with genome-scale metabolic models (GEMs) and flux balance analysis (FBA), have a look through the following article:
While genome-scale metabolic models may appear complicated and mysterious at first, they exist in our computers as modest text files. Analogous to the HTML format used to describe websites, the SBML format can be used to describe the metabolism of organisms.
- Read about the Systems Biology Markup Language (SBML) standard to familiarize yourself with the GEM format output of CarveMe.
The models we are using have been borrowed from the materials of a manuscript-in-preparation. Both models were reconstructed using CarveMe and manually curated to study the S. cerevisiae <-> L. lactis metabolic interactions. You can have a look at the python scripts (e.g. bacteria.py and yeast.py) to see how these models were manually curated.
Use less to view and scroll through the contents of the yeast model.
$ less $ROOT/models/yeast.xmlClick to see yeast model
<?xml version="1.0" encoding="UTF-8"?>
<sbml xmlns="http://www.sbml.org/sbml/level3/version1/core" level="3" version="1">
<model id="yeast_LB">
<listOfCompartments>
<compartment id="C_c" name="cytosol" size="1" constant="true"/>
<compartment id="C_p" name="periplasm" size="1" constant="true"/>
<compartment id="C_e" name="extracellular space" size="1" constant="true"/>
</listOfCompartments>
<listOfSpecies>
<species id="M_10fthf_c" name="10-Formyltetrahydrofolate" compartment="C_c" hasOnlySubstanceUnits="true">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<p>FORMULA: C20H21N7O7</p>
<p>BioCyc: META:10-FORMYL-THF</p>
<p>SEED Compound: cpd00201</p>
<p>UniPathway Compound: UPC00234</p>
<p>KEGG Compound: C00234</p>
<p>BioPath Molecule: 10-Formyl-5,6,7,8-tetrahydrofolate</p>
<p>MetaNetX (MNX) Chemical: MNXM237</p>
<p>Reactome: 419151;5389850</p>
<p>Human Metabolome Database: HMDB00972</p>
</html>
</notes>
</species>
<species id="M_adp_c" name="ADP" compartment="C_c" hasOnlySubstanceUnits="true">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<p>FORMULA: C10H12N5O10P2</p>
<p>BioCyc: META:ADP;META:ADP-GROUP</p>
<p>SEED Compound: cpd00008</p>
<p>UniPathway Compound: UPC00008</p>
<p>KEGG Compound: C00008;G11113</p>
<p>BioPath Molecule: Adenosine-5-prime-diphosphate</p>
<p>MetaNetX (MNX) Chemical: MNXM7</p>
<p>Reactome: 113581;113582;114565;211606;29370;5632457</p>
<p>Human Metabolome Database: HMDB01341</p>
</html>
</notes>
</species>
<species id="M_atp_c" name="ATP" compartment="C_c" hasOnlySubstanceUnits="true">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<p>FORMULA: C10H12N5O13P3</p>
<p>BioCyc: META:ATP</p>
<p>SEED Compound: cpd00002</p>
<p>UniPathway Compound: UPC00002</p>
<p>KEGG Compound: C00002;D08646</p>
<p>BioPath Molecule: Adenosine-5-prime-triphosphate</p>
<p>MetaNetX (MNX) Chemical: MNXM3</p>
<p>Reactome: 211579;389573</p>
<p>Human Metabolome Database: HMDB00538</p>
</html>
</notes>
</species>
...Press the q key to stop viewing the file.
Use less to view and scroll through the contents of the bacterial model.
$ less $ROOT/models/bacteria.xmlClick to see bacterial model
<?xml version="1.0" encoding="UTF-8"?>
<sbml xmlns="http://www.sbml.org/sbml/level3/version1/core" level="3" version="1">
<model id="cremoris_ref2">
<listOfCompartments>
<compartment id="C_c" name="cytosol" size="1" constant="true"/>
<compartment id="C_p" name="periplasm" size="1" constant="true"/>
<compartment id="C_e" name="extracellular space" size="1" constant="true"/>
</listOfCompartments>
<listOfSpecies>
<species id="M_10fthf_c" name="10-Formyltetrahydrofolate" compartment="C_c" hasOnlySubstanceUnits="true">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<p>FORMULA: C20H21N7O7</p>
<p>BioCyc: META:10-FORMYL-THF</p>
<p>SEED Compound: cpd00201</p>
<p>UniPathway Compound: UPC00234</p>
<p>KEGG Compound: C00234</p>
<p>BioPath Molecule: 10-Formyl-5,6,7,8-tetrahydrofolate</p>
<p>MetaNetX (MNX) Chemical: MNXM237</p>
<p>Reactome: 419151;5389850</p>
<p>Human Metabolome Database: HMDB00972</p>
</html>
</notes>
</species>
<species id="M_adp_c" name="ADP" compartment="C_c" hasOnlySubstanceUnits="true">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<p>FORMULA: C10H12N5O10P2</p>
<p>BioCyc: META:ADP;META:ADP-GROUP</p>
<p>SEED Compound: cpd00008</p>
<p>UniPathway Compound: UPC00008</p>
<p>KEGG Compound: C00008;G11113</p>
<p>BioPath Molecule: Adenosine-5-prime-diphosphate</p>
<p>MetaNetX (MNX) Chemical: MNXM7</p>
<p>Reactome: 113581;113582;114565;211606;29370;5632457</p>
<p>Human Metabolome Database: HMDB01341</p>
</html>
</notes>
</species>
<species id="M_atp_c" name="ATP" compartment="C_c" hasOnlySubstanceUnits="true">
<notes>
<html xmlns="http://www.w3.org/1999/xhtml">
<p>FORMULA: C10H12N5O13P3</p>
<p>BioCyc: META:ATP</p>
<p>SEED Compound: cpd00002</p>
<p>UniPathway Compound: UPC00002</p>
<p>KEGG Compound: C00002;D08646</p>
<p>BioPath Molecule: Adenosine-5-prime-triphosphate</p>
<p>MetaNetX (MNX) Chemical: MNXM3</p>
<p>Reactome: 211579;389573</p>
<p>Human Metabolome Database: HMDB00538</p>
</html>
</notes>
</species>
...Press the q key to stop viewing the file.
While this can be informative for some quick inspection, we may also visualize these metabolic models using web-based tools such as fluxer. Upload the bacteria and/or yeast model and have a look around!
Use paste to view the contents of the media.tsv file
$ paste $ROOT/media.tsvClick to see media file
Lines 1 to 172 in 3971c20
Search the BiGG database to learn more about specific metabolites name and identifiers.
If you are feeling adventurous, come up with your own media composition/variation for simulation to be used in the following exercise!
- What are GEMs and how can they be used? What is FBA? What is SBML?
- How many reactions and metabolites are present in the yeast model? What about the bacterial model?
- How were these models reconstructed? To what extent is there metabolic compartmentalization?
- What classes of metabolites are present in the media compositions? What is different across the media variations?
- Is the yeast model gapfilled on a particular media?
- What compound does the BiGG ID
pnto__Rrepresent?